(新加坡18日訊)新加坡科學家發現了人類幹細胞“百變”的秘密,而且只要啟動這個被稱為PRDM14的基因,任何普通細胞都有可能“變身”為幹細胞,成功率比現有技術高三倍。

 

擁有多能性(pluripotency)的胚胎幹細胞(embryonic stem cell),能變成人體裡200多種細胞中的任何一種,自我“繁殖”能力也強,因此一直被視為各種絕症的希望。

不過,由於牽涉道德問題,胚胎幹細胞研究一再受阻,科學家只好另覓良方。

科學人員近年就開始鑽研“培育”多能性幹細胞的可能性,通過“重新編排”(re-programme)改變細胞基因,讓普通細胞也具多能性。

由19名新加坡科學家組成的研究小組就花了3年,從2萬1千組基因中,找到了幹細胞“多能性”的重要鑰匙。這相信是有史至今,最大規模的幹細胞基因研究。

“添置”PRDM14基因  將培育三倍多能性細胞

負責率領小組的是新加坡科技研究局(A*Star)屬下的新加坡基因組研究院和份子與生物細胞研究院。小組的研究報告,剛於最新一期的國際頂尖學術期刊《自然》(Nature)刊登。

參與研究的新加坡基因組研究院高級研究小組組長黃學暉博士受訪時指出,要讓普通細胞具多能性,需啟動的基因有好幾組,PRDM14只是其中之一,但它卻也扮演著重要角色。

小組發現,在改造細胞時如果為細胞“添置”PRDM14基因組,那最終培育出具多能性的細胞,將比平日多出三倍。

此外,他們也發現PRDM14隻在人類的幹細胞中扮演重要角色,對老鼠幹細胞則不重要。這顯示了不同物種間幹細胞的差異,也再次彰顯了以人類細胞進行研究的重要性。

不過,黃博士坦誠,目前還不清楚這項發現能如何應用於醫藥治療。“除了PRDM14,我們目前還在研究很多其他的基因組。當中一些可能對個別病症具重要功能。”

“目前我們很難推算出一個時間表,正如很多重要的治療,從發現到最終的臨床應用是需要時間的。”

黃博士表示,目前一些常見的幹細胞療法用的都是他人捐贈的幹細胞,可是新的研究卻能直接用病人本身的細胞“培育”出幹細胞,彷彿是為病人“量身”制定,相信會更理想。

星洲日報/國際‧2010.10.18
 

Scientists First to Perform Genome-Wide Study of Human Stem Cells

Their research, published in the journal Nature, is the first ever genome-wide study of human stem cells on such a massive scale, and its results are crucial in understanding how stem cells may one day be used to treat debilitating conditions such as Parkinson's disease and traumatic spinal injury.

GIS Senior Group Leader for Stem Cell and Development Biology and Associate Director for Biology Dr Ng Huck Hui, and IMCB Principal Investigator Dr Frederic Bard combined the strengths of their teams to investigate the 21,000 genes in the entire human genome to find those which regulate the two characteristic properties of hESCs -- the capacity to turn into any type of cell in the human body (pluripotency), and the ability to retain that capacity indefinitely. Out of the several key genes they identified, a particular gene known as PRDM14 was discovered to make it easier to turn a type of human cell (fibroblasts) into pluripotent stem cells. The discoveries contribute to a fundamental understanding of the nature of stem cells and helps efforts to improve techniques to turn mature adult cells into hESCs.

In addition, the scientists found that PRDM14 played a key role in hESCs, but not in mouse ESCs. This significant new finding highlights the fundamental differences between stem cells from different species, and highlights the greater need to use human cells in stem cell research.

"Very little is known about the molecular machines that drive stem cell states or the transcriptional profiles of hESCs. Our study helps to build a better understanding of hESCs and this will help in the development of technologies to further the utilities of these cells such as their potential to be used for clinical and therapeutic applications," said Dr Ng. "Dr Bard's scientific expertise was invaluable in helping us crack another piece of the stem cell puzzle. I definitely look forward to collaborating with him on more projects that aim to peel away the mysteries surrounding stem cells" he added.

Dr Alan Colman, Executive Director of the Singapore Stem Cell Consortium, said, "Huck Hui Ng and his colleagues continue to keep Singapore at the top table of countries plundering the secrets of human embryonic stem cell regulation. This time they have deployed the first genome-wide functional screen to identify factors that maintain 'stemness' in these cells and yet again reveal major differences between mouse and human embryonic stem cells in the control of this important property."

Senior Scientist at the Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Dr Janet Rossant added, "The unprecedented scale of this screen has added considerable new information to our understanding of pluripotency and will help efforts to improve reprogramming of adult cells."

Professor Lee Eng Hin, Executive Director of the Biomedical Research Council, A*STAR, applauded the discovery and said, "This is an examplar of a great cross institutional collaboration. The combined strength of stem cell and genomics experts has led to a great piece of world-class work. I hope to see more of such valuable partnerships in the future."

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